We propose a continuation and expansion of our current investigation into the science and engineering of elasticity imaging for improved breast cancer diagnosis and treatment. Our central hypothesis is that ultrasound offers unique opportunities to image key structural, functional and compositional properties of breast tissue in vivo. Recent advances in cellular and molecular biology are revealing the mechanisms by which tissues alter their architecture during tumor formation, and have spawned an array of new treatment strategies that can only be evaluated in vivo. Increases in regional vessel density, focal fibrosis, and desmoplasia are specific early indicators of neoplasia and metastatic potential that can be followed using ultrasonic methods. Developments in targeted therapeutics require new imaging techniques that allow investigators to conduct serial studies throughout the progression of disease. Phantom and patient studies will be conducted to validate the approach and discover diagnostic opportunities. We propose a plan to expand our investigation of elastic properties of tissues to include methods for imaging viscoelasticity, in vivo. The five-year plan is designed around four specific aims: (1) develop new viscoelasticity imaging techniques, (2) model viscoelastic properties of tissues from analysis of hydrogel measurements, (3) conduct a Phase II clinical trial, and (4), investigate image quality features. The intent is to develop new in vivo ultrasonic imaging techniques that describe the tumor microenvironment in ways that identify aggressive breast cancers early in development.